Supplementary Material for: Isolated non-secretory extramedullary relapse of multiple myeloma responded completely to localized radiotherapy

INTRODUCTION: Non-secretory multiple myeloma (NSMM) is a rare form of multiple myeloma (MM) that is often difficult to detect and has not yet been well characterised. This is due to the lack of production or the presence of monoclonal proteins levels below levels detectable by testing such as serum/urine electrophoresis (SPEP/UPEP) and immunofixation.
CASE PRESENTATION: Two patients of ours were being treated for MM with typical courses of systemic therapy. By the 3rd line therapy, both developed an extramedullary mass, one in the pelvis and the other in the neck. In both cases blood work showed no measurable monoclonal protein (MP), normal free light chain levels and unremarkable skeletal surveys. Secondary malignancies were suspected due to the clinical presentation in each case, and biopsies confirmed the presence of non-secretory plasmacytomas. Both patients were only treated with localized radiotherapy with a total dose of 2000 cGy in 5 fractions over 1 week. Ultimately, this resolved the original masses with no residual tumours. No changes had to be made to their systemic therapies, and both patients remain stable in remission.
CONCLUSION: Non-secretory multiple myeloma relapse is not unusual and should be suspected in patients with relapsed refractory disease. Relapse should be confirmed by a tissue biopsy, and secondary malignancies should be ruled out. Radiotherapy is an excellent option to treat localized relapse and preserve the current line of systemic anti-myeloma therapy.

引言：非分泌型多发性骨髓瘤（Non-secretory multiple myeloma, NSMM）是多发性骨髓瘤（multiple myeloma, MM）的罕见亚型，通常难以检出且尚未得到充分阐明。其发病机制与瘤细胞无法分泌单克隆蛋白，或单克隆蛋白水平低于血清/尿蛋白电泳（serum/urine electrophoresis, SPEP/UPEP）及免疫固定电泳等检测手段的可检测阈值有关。

病例介绍：本团队收治的2例多发性骨髓瘤患者，均接受了标准系统性治疗方案。至三线治疗阶段，二人均出现髓外肿块：一例位于盆腔，另一例位于颈部。两例患者的血液检查均未检出可测量的单克隆蛋白（monoclonal protein, MP），游离轻链水平正常，骨骼影像学检查无异常表现。结合临床症状，临床首先怀疑为继发性恶性肿瘤，后续活检证实为非分泌型浆细胞瘤。两名患者仅接受局部放射治疗，总剂量为2000 cGy，分5次给药，疗程历时1周。最终原发病灶完全消退，无残留肿瘤。无需调整其系统性治疗方案，两名患者目前均处于稳定缓解状态。

结论：非分泌型多发性骨髓瘤复发并不少见，对于复发难治性患者应高度警惕该病症。复发需通过组织活检确诊，并需排除继发性恶性肿瘤。放射治疗是治疗局部复发的极佳选择，可维持当前系统性抗骨髓瘤治疗方案的连续性。